title: Structure-activity relationships of an antimicrobial peptide plantaricin s from two-peptide class IIb bacteriocins.
abstract: Class IIb bacteriocins are ribosomally synthesized antimicrobial peptides comprising two different peptides synergistically acting in equal amounts for optimal potency. In this study, we demonstrate for the first time potent (nanomolar) antimicrobial activity of a representative class IIb bacteriocin, plantaricin S (Pls), against four pathogenic gram-positive bacteria, including Listeria monocytogenes. The structure-activity relationships for Pls were studied using activity assays, circular dichroism (CD), and molecular dynamics (MD) simulations. The two Pls peptides and five Pls derived fragments were synthesized. The CD spectra of the Pls and selected fragments revealed helical conformations in aqueous 2,2,2-trifluoroethanol. The MD simulations showed that when the two Pls peptides are in antiparallel orientation, the helical regions interact and align, mediated by strong attraction between conserved GxxxG/AxxxA motifs. The results strongly correlate with the antimicrobial activity suggesting that helix-helix alignment of the two Pls peptides and interaction between the conserved motifs are crucial for interaction with the target cell membrane.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, T6G 2N8, Canada.
authors.forename: Wael
authors.initials: W
authors.lastname: Soliman
authors.forename: Liru
authors.initials: L
authors.lastname: Wang
authors.forename: Subir
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Kamaljit
authors.initials: K
authors.lastname: Kaur
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001430:Bacteriocins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D001430:Bacteriocins; D008051:Lipid Bilayers; D010446:Peptide Fragments